Remember Gilead, that wicked company that dared to cure hepatitis C and made a bunch of money doing so? If this doesn't ring a bell, go back a couple of decades. Perhaps you'll remember the company's anti-HIV drugs, you know, the ones that have essentially removed the term "AIDS" from the American vernacular (1) and are expected to completely end all new infections and deaths in Africa by 2030.

But despite four decades of research and one failed vaccine after another, AIDS has not been cured, only controlled. People who are HIV-positive must still take antiretroviral drugs for the rest of their lives to suppress the virus. But that could finally change. Gilead put a whole lot of that money back into research and, in doing so, may eventually "put themselves out of business." That's a bit optimistic for the moment, however, Gilead in conjunction with the Beth Israel Deaconess Medical Center have done something new, which at least suggests that HIV could one day be cured.

At the recent Conference on Retroviruses and Opportunistic Infections in Boston, Dan Barouch, M.D., Ph.D of Beth Israel spoke about an unprecedented advance in controlling HIV. By combining an antibody called PGT121 with Gilead's GS-9620 TLR7 agonist (2), a direct acting antiretroviral experimental drug, some remarkable results were seen in rhesus macaques that had been infected an HIV-like virus that also infects monkeys. Some of the monkeys (5 of 11) remained "virus free" (3) 168 days after the drug combination was stopped. This has never happened before.

The job of GS-9620 is to force latent HIV from their immune cell reservoir. Then PGT121 can attach to the virus and clear it from the blood. If it sounds like both drugs are needed it's because they are. Neither drug alone did much of anything. The binding of GS-9620 to the TLR7 receptor is shown in Figure 1.

Figure 1. Left: The chemical structure of GS-9620. Center: GS-9620 bound to the TLR7 receptor. Right: A close up of the GS-9620 at its binding site. Note the very good fit between the drug (magenta) and the receptor (receptors are proteins.) The letters are abbreviations for the amino acids that form the protein. Each of the 20 amino acids that are the building block of proteins has its own abbreviation. For example, Y means tyrosine, V means valine, etc. The numbers refer to the linearposition of the amino acid in the protein. So, D555 means that an aspartic acid is found in the 555th position from the end of the protein chain. But proteins are three-dimensional and they twist, turn and fold. The position of amino acids within the chain tells nothing about the size or shape of the protein. Source: " Molecular Determinants of GS-9620-Dependent TLR7 Activation" PLOS ONE, January 2016

Even if things go perfectly we are still (at best) years from a cure, but the synergistic effect of these two drugs provides "proof of concept," a critically important milestone in drug development. Meanwhile, Gilead isn't sitting still. The company discovered GS-9722, a different antibody that may be superior to PGT121, which is now in Phase I trials, as is the GS-9620-PGT121 combination.

Good for them. You too.

NOTES:

(1) In 2014, the last year with complete records, there were 6,721 deaths directly attributable to HIV in the US 2014, an 86% reduction from 1995, the worst year on record.

(2) TLR7 is short for Toll-like receptor 7. When the receptor is activated (this is the function of GS-9620) it forces HIV out of reservoirs in immune cells. Then the antibody can clear the virus from the blood.

(3) "Virus free" is an expression which is not technically correct. It refers to levels of HIV that are so low that they cannot be measured.

Dr. Josh Bloom, the Director of Chemical and Pharmaceutical Science, comes from the world of drug discovery, where he did research for more than 20 years. The field of drug discovery involves chemistry, biochemistry, toxicology, and pharmacology - skills that he has used to write on a wide variety of topics since he joined ACSH in 2010. One of the topics he has tackled is the so-called "opioid crisis." He is now recognized as an expert in this area and was the first journalist to write a nationally published opinion piece about the unintended consequences of a governmental crackdown on prescription pain medications (New York Post, 2013). Since that time he has published more than 20 op-eds in regional and national newspapers on different aspects of the crisis. In that same year, he testified at an FDA hearing, where he noted that fentanyl was the real danger, something that would be proven years later. At that time almost no one had heard of the drug.

He was also the first writer (2016) to study, dissect and ultimately debunk the manipulated statistics used by the CDC to justify its recommendations for opioid prescribing, which have resulted in Draconian requirements for prescribing pain medications as well as government-mandated, involuntary tapering of patients receiving opioid treatment, both of which have caused great harm and needless suffering to chronic pain patients. His 2016 article, "Six Charts Designed to Confuse You," is the seminal work on CDC deception and has been adopted by patient advocacy groups and individuals and has been sent to governors and state legislatures.

Dr. Bloom earned his Ph.D. in organic chemistry from the University of Virginia, followed by postdoctoral training at the University of Pennsylvania. His career in drug discovery research began at Lederle Laboratories, which was acquired by Wyeth in 1994, which itself was acquired by Pfizer in 2009. During this time he participated in research in a number of therapeutic areas, including diabetes and obesity, antibiotics, HIV/AIDS, hepatitis C, and oncology. His group discovered the novel antibiotic Tygacil®, which was approved by the FDA for use against resistant bacterial infections in 2005. He is the author of 25 patents, and 35 academic papers, including a chapter on new therapies for hepatitis C in Burger’s Medicinal Chemistry, Drug Discovery and Development, 7th Edition (Wiley, 2010), and has given numerous invited lectures about how the pharmaceutical industry really works.

Dr. Bloom joined the American Council on Science and Health in 2010 as ACSH’s Director of Chemical and Pharmaceutical Sciences, and has since published more than 60 op-eds in numerous periodicals, including The Wall Street Journal, Forbes, New Scientist, The New York Post, National Review Online, The Boston Herald, and The Chicago Tribune, and given numerous radio and television interview on topics related to drugs and chemicals. In 2014, Dr. Bloom was invited to become a featured writer for the site Science 2.0, where he wrote more 75 pieces on a broad range of topics.

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